It is essential that scientists in each of the projects be able to upregulate and downregulate the activity of key proteins and to analyze mutants thereof. This core will provide three services: (1) generation of retrovirus vectors expressing both wild type and mutant alleles of key proteins (2) construction of DNA based vectors for the generation of small interfering RNAs to key genes and (3) continuing technology development for (1) and (2). Taken together the first two functions will allow program members to rapidly assess the effects of either loss of function of gain of function in any gene of interest. Since the technologies involved are in rapid flux, the third role of the core is to act as a technology development center for the program to insure the most facile methods are continuously available.